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Biomedical subjects

J Dionne

Publications and source records attributed to J Dionne.

13 recordsLinked to original sources
PubMed2000

Oestradiol decreases rat apolipoprotein AI transcription via promoter site B.

Oestrogens protect against ischaemic heart disease in the post-menopausal female by increasing serum concentrations of apolipoprotein (apo) AI and the abundance of high-density lipoprotein particles. In men and experimental male animals, the administration of oestrogen has variable effects on apo AI expression. As the major mode of oestrogen action on target genes involves regulating promoter activity and hence transcription, oestrogen is expected to alter transcription of the apo AI gene. To test this hypothesis, the effect of 17beta-oestradiol (E(2)), on rat apo AI promoter activity in male hepatoma HuH-7 cells, was tested by co-transfecting a reporter template, pAI.474.CAT containing-474 to-7 of the rat apo AI promoter and an oestrogen receptor (ER) expression vector, pCMV-ER. Transfected cells exposed to E(2) showed a dose-dependent decrease in chloramphenicol acetyltransferase (CAT)-activity, with a maximum 91+/-1.5% reduction at 1 microM E(2). Deletional analysis of the promoter localized the inhibitory effect of ER and E(2) to site B (-170 to-144) with an adjacent 5' contiguous motif, site S (-186 to-171) acting as an amplifier. HuH-7 cell nuclear extracts showed binding activities with both sites S and B, but recombinant human ER did not. Furthermore, nuclear extracts from E(2)-treated HuH-7 cells showed weaker binding activity to site B, but not to site S. In summary, the inhibitory effect of ER and E(2) on rat apo AI gene activity is mediated by a promoter element, site B. This inhibitory effect arises from a mechanism that does not involve direct ER binding to the B-element. The conclusion that E(2) inhibits apo AI transcription was confirmed in vivo. Treatment of male adult Sprague-Dawley rats with up to 200 microg E(2) for 7 days decreased apo AI protein and hepatic mRNA by 72+/-21% and 68+/-1.4% respectively. Results of 'run-on' transcription of the apo AI gene in isolated hepatic nuclei showed a 55% decrease in hormone-treated male rats. These findings suggest that E(2) exerts primarily an inhibitory effect within male hepatic nuclei.

Animals↗
PubMed1997

Pilot phase I-II study on 5-aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer.

5-Aza-2'-deoxycytidine (5-AZA-CdR, Decitabine) is a nucleoside analog and an active drug for the therapy of acute leukemia. The incorporation of 5-AZA-CdR into DNA blocks DNA methylation and can result in the activation of specific genes, such as tumor suppressor genes. This novel mechanism of action of 5-AZA-CdR stimulated our interest in its potential for cancer therapy in patients with lung cancer. Using a colony assay we observed that 5-AZA-CdR showed a potent antineoplastic effect against two human lung carcinoma cell lines. The objective of this preliminary phase I-II study was to evaluate the toxicity and clinical efficacy of 5-AZA-CdR in patients with stage IV non-small cell lung carcinoma. There were 15 patients that entered the clinical study. For nine assessable patients that received 5-AZA-CdR by a single 8 h i.v. infusion of 200-660 mg/m2 for one or more cycles, the median survival duration was 6.7 months, with three patients surviving more than 15 months. The steady-state plasma concentration of 5-AZA-CdR during the infusion was estimated in some patients and was in the same range that produced activation of a tumor suppressor gene in human lung tumor cell lines as reported by other investigators. The major side effect of 5-AZA-CdR was hematopoietic toxicity which required a 5-6 week recovery period before the next cycle of therapy. This study suggests that 5-AZA-CdR may have some clinical activity against metastatic lung carcinoma using this type of dose schedule.

Adult↗
PubMed1995

Improved adenovirus vector provides herpes simplex virus ribonucleotide reductase R1 and R2 subunits very efficiently.

We have constructed a new adenovirus (Ad) expression vector, pAdBM5, that allows for the production of unprecedented levels of recombinant protein in the human 293 cell line using the Ad expression system. The main feature of this vector is a combination of enhancer sequences that increases the activity of the ectopic major late promoter (MLP) in recombinant Ad. In 293 cells infected with helper-free Ad recombinants generated with the pAdBM5 transfer vector, both herpes simplex virus (HSV) ribonucleotide reductase R1 and R2 subunits represent the most abundant polypeptides, accounting for as much as 15-20% of total cellular proteins. Our data suggest that this level of expression is probably very close to the upper limit of the system. Furthermore, when compared to the widely utilized baculovirus (Bac)/Sf9 expression system, the improved Ad vector showed a better performance for the production and purification of active HSV-2 ribonucleotide reductase R1 and R2 subunits. The R2 subunit was about 5-fold more abundant in recombinant Ad-infected 293 cells than in Bac-infected Sf9 cells while the R1 subunit was produced at roughly similar levels with either system. However, the amount of active soluble R1 obtained from recombinant Ad-infected 293 cells was at least 5 times higher because most of the R1 produced in Sf9 cells was insoluble.

Adenoviruses, Human↗
PubMed1994

The importance of dose scheduling with mitoxantrone, 5-fluorouracil and leucovorin in metastatic breast cancer.

We have studied a mitoxantrone, 5-fluorouracil (5-FU) and leucovorin chemotherapy regimen in metastatic breast cancer. 8 patients received mitoxantrone 10 mg/m2 on day 1, leucovorin 200 mg/m2 and 5-FU 300 mg/m2 on days 1-5 by intravenous bolus every 28 days in a pilot study. Grades 3-4 granulocytopenia followed 55% of the courses, with 2 patients admitted for febrile neutropenia. Only a 29% objective response rate was seen in a subsequent phase II trial using reduced mitoxantrone doses. Comparison with other trials suggested that 5-day bolus 5-FU administration adversely affects the combination's therapeutic index.

Adenocarcinoma↗
PubMed1990

Identification and sequencing of the spheroidin gene of Choristoneura biennis entomopoxvirus.

Entomopoxviruses are a class of insect viruses whose virions are embedded in cytoplasmic occlusion bodies. The major component of these protective complexes is a protein called spheroidin. An open reading frame encoding the spheroidin gene of Choristoneura biennis entomopoxvirus has been identified and sequenced in our laboratory. This protein coding region is 1023 nucleotides long and specifies a polypeptide of 38,500 Da. Spheroidin was purified by SDS polyacrylamide gel electrophoresis, electroeluted, and its amino terminus sequence was determined on a gas phase sequencer. We observed that the first 20 N-terminal amino acids were absent in the mature processed form of the spheroidin molecule. Examination of these 20 residues revealed their hydrophobic nature and close resemblance to the consensus signal peptide sequence which is commonly found on membrane proteins. The DNA sequence of the spheroidin gene predicted a processed polypeptide with a molecular weight of 36 kDa. However, spheroidin was observed to aggregate in complexes composed of 50-kDa monomers. Intermolecular disulfide bonds were shown to play major roles in the formation and structure of these viral occlusion bodies. The difference in molecular weight between the predicted protein and its counterpart in infected cells is likely due to post-translational modifications. Indeed, two potential asparagine-linked glycosylation sites are present on the spheroidin molecule. The 5' flanking regions of the spheroidin gene and the vaccinia major core protein precursor gene P4b were shown to share substantial homology.

Amino Acid Sequence↗
PubMed1985

Cochleosacculotomy.

In 1982 and 83, we performed cochleosacculotomies on 12 patients, of which nine have been retained for the present study. The operation was carried out on patients affected by unilateral Ménière's disease with a hearing loss stabilized at 50 dB or more at speech frequencies. All patients were suffering incapacitating vertigo which was perfectly controlled in all the cases operated so far. On the other hand, the hearing results were much les satisfactory in that eight of the nine cases had no serviceable hearing after the operation. It is concluded that, in our hands so far, this cannot be considered as a conservative surgical procedure, but it is an alternative for the control of vertigo in Ménière's disease.

Audiometry, Pure-Tone↗
PubMed1979

Oculomotor and vestibular findings in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Electronystagmographic recordings were made of oculomotor and vestibular function in 11 patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay. All had horizontal gaze nystagmus, marked impairment of smooth ocular pursuit and optokinetic nystagmus, and defective fixation suppression of caloric nystagmus. Many had saccadic dysmetria, but saccade velocity was probably unaffected. Abnormalities pointing to brainstem disturbance were sparse. The findings are thought to indicate mainly diffuse cerebellar disease, with particular involvement of vermis and vestibulo-cerebellum.

Adolescent↗
PubMed1977

[Complications in rhinoseptoplasty].

We have done a survey of our first 115 cases of rhinoseptoplasty. We noticed that 19 per cent of the patients presented partial nasal obstruction following first surgery, thus requiring a second surgical procedure. We attempt to suggest a few causes of this high percentage of failures and suggest some technical modifications to avoid such complications.

Atrophy↗